Characterizing Frontal Lobe Seizure Semiology in Children.

OBJECTIVE: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. METHODS: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). RESULTS: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). INTERPRETATION: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.

Optimizing Surgical Planning for Epilepsy Patients With Multimodal Neuroimaging and Neurophysiology Integration: A Case Study.

SUMMARY: Current preoperative evaluation of epilepsy can be challenging because of the lack of a comprehensive view of the network's dysfunctions. To demonstrate the utility of our multimodal neurophysiology and neuroimaging integration approach in the presurgical evaluation, we present a proof-of-concept for using this approach in a patient with nonlesional frontal lobe epilepsy who underwent two resective surgeries to achieve seizure control. We conducted a post-hoc investigation using four neuroimaging and neurophysiology modalities: diffusion tensor imaging, resting-state functional MRI, and stereoelectroencephalography at rest and during seizures. We computed region-of-interest-based connectivity for each modality and applied betweenness centrality to identify key network hubs across modalities. Our results revealed that despite seizure semiology and stereoelectroencephalography indicating dysfunction in the right orbitofrontal region, the maximum overlap on the hubs across modalities extended to right temporal areas. Notably, the right middle temporal lobe region served as an overlap hub across diffusion tensor imaging, resting-state functional MRI, and rest stereoelectroencephalography networks and was only included in the resected area in the second surgery, which led to long-term seizure control of this patient. Our findings demonstrated that transmodal hubs could help identify key areas related to epileptogenic network. Therefore, this case presents a promising perspective of using a multimodal approach to improve the presurgical evaluation of patients with epilepsy.

Oral and manual automatisms elicited by electrical stimulation of the pars opercularis cortex in a patient with frontal lobe epilepsy.

Oral automatism (OA) and manual automatism (MA) are common signs during initiation of temporal seizures. However, the precise symptomatogenic zones for OA and MA remains largely unclear. In this study, we presented a case of intractable frontal lobe epilepsy (FLE) in which the patient received intracranial EEG monitoring with subdural electrodes. During electrical stimulation of a grid contact located over the right pars opercularis cortex, OA and contralateral MA were observed unexpectedly without afterdischarges (ADs) or with brief ADs detected in the adjacent contacts. This case suggested that the pars opercularis cortex might play an important role in generating OA. In addition, our data implied that the symptomatogenic zone for MA might locate contralaterally to symptomatic hand.

How cerebral cortex protects itself from interictal spikes: The alpha/beta inhibition mechanism.

Interactions between interictal epileptiform discharges (IEDs) and distant cortical regions subserve potential effects on cognition of patients with focal epilepsy. We hypothesize that "healthy" brain areas at a distance from the epileptic focus may respond to the interference of IEDs by generating inhibitory alpha and beta oscillations. We predict that more prominent alpha-beta oscillations can be found in patients with less impaired neurocognitive profile. We performed a source imaging magnetoencephalography study, including 41 focal epilepsy patients: 21 with frontal lobe epilepsy (FLE) and 20 with mesial temporal lobe epilepsy. We investigated the effect of anterior (i.e., frontal and temporal) IEDs on the oscillatory pattern over posterior head regions. We compared cortical oscillations (5-80 Hz) temporally linked to 3,749 IEDs (1,945 frontal and 1,803 temporal) versus an equal number of IED-free segments. We correlated results from IED triggered oscillations to global neurocognitive performance. Only frontal IEDs triggered alpha-beta oscillations over posterior head regions. IEDs with higher amplitude triggered alpha-beta oscillations of higher magnitude. The intensity of posterior head region alpha-beta oscillations significantly correlated with a better neuropsychological profile. Our study demonstrated that cerebral cortex protects itself from IEDs with generation of inhibitory alpha-beta oscillations at distant cortical regions. The association of more prominent oscillations with a better cognitive status suggests that this mechanism might play a role in determining the cognitive resilience in patients with FLE.

Sleep-related hypermotor epilepsy associated mutations uncover important kinetic roles of α4ß2- nicotinic acetylcholine receptor intracellular structures.

Sleep-related hypermotor epilepsy (SHE) is a group of seizure disorders prominently associated with mutations in nicotinic acetylcholine receptors (nAChR). The most prevalent central nervous system nAChR subtype contains α4 and ß2 subunits, in two ratios. (α4ß2)2ß2-nAChR have high agonist sensitivity (HS-isoform), whereas (α4ß2)2α4-nAChR agonist responses exhibit a small high-sensitivity, and a predominant low-sensitivity, phase of function (LS-isoform). Multiple non-synonymous mutations in the second and third transmembrane domains of α4 and ß2 subunits are associated with SHE. We recently demonstrated that two additional, SHE-associated, missense mutations in the major cytoplasmic loops of these subunits [α4(R336H) and ß2(V337G)] cause increased macroscopic function-per receptor. Here, we use single-channel patch-clamp electrophysiology to show that these mutations influence single-channel amplitudes and open- and closed-state kinetics. Pure populations of HS- or LS-isoform α4ß2-nAChR were expressed by injecting either 1:10 or 30:1 α4:ß2 cRNA ratios, respectively, into Xenopus laevis oocytes. Functional properties of the resulting mutant α4ß2-nAChR isoforms were compared to their wildtype counterparts. α4(R336H) subunit incorporation minimally affected single-channel amplitudes, whereas ß2(V337G) subunit incorporation reduced them significantly in both isoforms. However, for both mutant subunits, increased function-per-receptor was predominantly caused by altered single channel kinetics. The α4(R336H) mutation primarily destabilizes desensitized states between openings. By contrast, the ß2(V337G) mutation principally stabilizes receptor open states. The use of naturally-occurring and physiologically-impactful mutations has allowed us to define valuable new insights regarding the functional roles of nAChR intracellular domains. Further mechanistic context is provided by intracellular-domain structures recently published for other members of the Cys-loop receptor superfamily (α3ß4-nAChR and 5-HT3AR).

Multimodal neurocognitive markers of frontal lobe epilepsy: Insights from ecological text processing.

The pressing call to detect sensitive cognitive markers of frontal lobe epilepsy (FLE) remains poorly addressed. Standard frameworks prove nosologically unspecific (as they reveal deficits that also emerge across other epilepsy subtypes), possess low ecological validity, and are rarely supported by multimodal neuroimaging assessments. To bridge these gaps, we examined naturalistic action and non-action text comprehension, combined with structural and functional connectivity measures, in 19 FLE patients, 19 healthy controls, and 20 posterior cortex epilepsy (PCE) patients. Our analyses integrated inferential statistics and data-driven machine-learning classifiers. FLE patients were selectively and specifically impaired in action comprehension, irrespective of their neuropsychological profile. These deficits selectively and specifically correlated with (a) reduced integrity of the anterior thalamic radiation, a subcortical structure underlying motoric and action-language processing as well as epileptic seizure spread in this subtype; and (b) hypoconnectivity between the primary motor cortex and the left-parietal/supramarginal regions, two putative substrates of action-language comprehension. Moreover, machine-learning classifiers based on the above neurocognitive measures yielded 75% accuracy rates in discriminating individual FLE patients from both controls and PCE patients. Briefly, action-text assessments, combined with structural and functional connectivity measures, seem to capture ecological cognitive deficits that are specific to FLE, opening new avenues for discriminatory characterizations among epilepsy types.

SEEG re-exploration in a patient with complex frontal epilepsy with rapid perisylvian propagation and mixed "startle - reflex" seizures.

The SEEG International Course, organised in 2017, focused on the investigation and surgery of insulo-perisylvian epilepsies. We present one representative complex case that was discussed. The patient had seizures displaying startle/reflex components. He was MRI negative, while other non-invasive investigations offered only partially concordant data. Initial SEEG exploration resulted in an incomplete definition of the epileptogenic zone. A second SEEG followed, which led to a thorough assessment of the seizure onset zone and the epileptic network, localised to the lateral inferior premotor cortex, explaining the incongruent data obtained beforehand. This was the basis of a tailored resection with a favourable outcome. The patient has been seizure-free for five years without any motor nor cognitive deficits, but with pharmacodependence to one AED. The electroclinical reasoning is presented, accompanied by relevant commentaries and recommendations from the tutors [Published with video sequences].

Different faces of frontal lobe epilepsy: The clinical, electrophysiologic, and imaging experience of a tertiary center.

OBJECTIVE: Frontal lobe epilepsy (FLE) is the second most common epilepsy among drug-resistant focal epilepsies. Semiologic and electrophysiologic features of FLE present some difficulties because frontal lobe seizures are brief, accompanied by complex motor activities and emotional signs. The rich connectivity of the frontal lobe with other areas leads to the rapid and widespread propagation of seizure activity, which contribute to the difficulty of evaluating the semiologic and EEG patterns of the seizure. In this study, we investigated semiologic, interictal, ictal, and postictal EEG characteristics; the imaging data of patients with FLE and the possible contribution of these data to localization and lateralization of seizures. MATERIALS AND METHODS: The medical records of patients who were diagnosed as having FLE between 2010 and 2019 in our clinic were evaluated retrospectively. The diagnosis of FLE was considered either when patients had a structural lesion in the frontal region or seizure semiology and EEG characteristics were compatible with FLE. Clinical, electrophysiologic, and imaging features were investigated in these patients. RESULTS: We have evaluated 146 seizures in 36 patients (17 lesional and 19 non-lesional according to MRI). There were 110 focal motor or nonmotor seizures, 18 bilateral tonic-clonic seizures, and 18 subclinical seizures. There were 16 patients with aura. The most common semiologic feature was hyperkinetic movements. Among the interictal EEGs, 30.5 % included focal anomalies. Among the ictal EEGs, 69.1 % were non-localizing or lateralizing. The most common ictal pattern was rhythmic theta activity (21.2 %). In four patients, who had non-localizing or lateralizing EEG, the postictal EEG was informative. Our study showed a low percentage of localized FDG-PET, which, however, involved visual analysis. CONCLUSION: Our results support the previously known difficulties in the determination of the epileptogenic zone of FLE. Semiologic and electrophysiologic correlation studies, longer postictal records, and quantitative analysis of FDG-PET may contribute to a better characterization of the disease.

Television-induced electronegative photoparoxysmal response: an extratemporal seizure mimic?

Video-EEG monitoring is an established gold-standard procedure for diagnosis and differentiation of epileptic and non-epileptic seizures. Epilepsy misdiagnosis, to which factors such as EEG artifact misinterpretation contribute to, is common, and can have long-lasting iatrogenic repercussions to the clinical management of affected patients. Among the many types of responses to photic stimulation, artifacts and physiologic and epileptic responses are possible. All of these can interfere with EEG interpretation when provoked by a source of illumination. Photic-induced responses are of increasing relevance given the ubiquity of screens and other light-emitting electronics in our modern world. One of these, the photoparoxysmal response, is a frequent finding in photosensitive patients with genetic generalized epilepsies. Various responses beyond abnormal occurrence of cortical spikes or spike-and-wave discharges are known to occur on EEG in response to intermittent photic stimulation (IPS), with different clinical implications. To our knowledge, we report a unique electronegative photoparoxysmal response during video-EEG monitoring induced by fluctuating illumination caused by a distant television screen. This response mimicked an extratemporal seizure in a young woman with frontal lobe epilepsy, admitted for presurgical evaluation. Novel electronegative responses to electronic devices during video-EEG monitoring merit consideration by EEG interpreters to help avoid misdiagnosis.

Hyperkinetic Seizures with Ictal Fear as Localizing Ictal Signs in MRI-Negative Medial Frontal Lobe Epilepsy.

PURPOSE: Hyperkinetic seizures are described as seizure onset in the frontal or temporal lobe. Additional localizing information is important for diagnostic workup and surgical therapy. We describe diagnostic workup and surgical outcomes in three patients with pharmacoresistant focal emotional seizures with hyperkinetic elements. METHODS/RESULTS: High-resolution 3 Tesla (T) magnetic resonance imaging (MRI) did not reveal clear-cut lesions. Invasive video-electroencephalography (EEG) with depth electrodes along the cingulate sulcus (bilateral; patients 1 and 3), right; patient 2 provided congruent results for a circumscribed seizure onset zone within the medial frontal lobe (right: patients 1 and 2; left: patient 3). Topectomies were performed in all patients. Histopathology revealed a small focal cortical dysplasia in the three cases (focal cortical dysplasia [FCD] IIA: patient 1; FCD IIB: patients 2 and 3). All patients remained completely seizure-free since surgery (Engel 1A; follow-up: 9-28 months). CONCLUSION: Ictal fear associated with hyperkinetic semiology points to a seizure-onset zone within the anteromedial frontal lobe (anterior cingulate gyrus). Ictal semiology is crucial for the placement of depth electrodes, especially in MRI-negative cases. These cases illustrate a clinical advantage to the new International League against Epilepsy (ILAE) seizure classification, emphasizing initial clinical symptoms.

Heart rate variability in frontal lobe epilepsy: Association with SUDEP risk.

OBJECTIVES: Frontal lobe epilepsy (FLE) may impair autonomic heart rate modulation. Decreased heart rate variability (HRV) may enhance risk of sudden death. Our objective was to describe whole day and wakefulness/sleep HRV parameters from FLE patients in comparison with those of healthy controls and correlate HRV parameters to SUDEP-7 scores. METHODS: Ten patients with FLE and 15 healthy controls underwent a 24-hour electrocardiogram holter. The SUDEP-7 score was calculated for patients. Subgroups were identified according to active epilepsy, number of generalized seizures, cognitive deficit, medication load, and time-length of epilepsy. Time-domain SDNN, SDNNi, SDANN, rMSDD, and pNN50 and frequency-domain LF, HF, and LF/HF parameters were analyzed. Wilcoxon and Spearman correlation tests were used. A P < .05 was considered significant. RESULTS: Patients SDNN, SDNNi, rMSSD, and pNN50 were decreased in 24-hour recordings. Although a tendency for a protective effect of sleep was seen for both patients and controls, intragroup comparisons of sleeping/waking states revealed a significant increase in sleep rMSSD (P = .046) and pNN50 (P = .041) only for controls. All 24-hour time-domain parameters and LF were inversely and significantly correlated to SUDEP-7, particularly SDANN (ρ = -0.896, P = .00019), known to deteriorate with diminished physical activity and decreased in patients with more generalized seizures. Wakefulness parameters did not correlate to SUDEP-7, whereas correlations to sleep parameters were very strong, particularly with rMSSD (ρ = -0.945, P = .00012). Cognitive deficit was associated with decreased pNN50, sleep pNN50, and LH. CONCLUSION: HRV is impaired in patients with FLE. Low HRV scores are associated with increased risk for SUDEP as measured by the SUDEP-7 score.

Temporal variability profiling of the default mode across epilepsy subtypes.

OBJECTIVE: Epilepsies are a group of neurological disorders sharing certain core features, but also demonstrate remarkable pathogenic and symptomatic heterogeneities. Various subtypes of epilepsy have been identified with abnormal shift in the brain default mode network (DMN). This study aims to evaluate the fine details of shared and distinct alterations in the DMN among epileptic subtypes. METHODS: We collected resting-state functional magnetic resonance imaging (MRI) data from a large epilepsy sample (n = 371) at a single center, including temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and genetic generalized epilepsy with generalized tonic-clonic seizures (GGE-GTCS), as well as healthy controls (HC, n = 150). We analyzed temporal dynamics profiling of the DMN, including edge-wise and node-wise temporal variabilities, and recurrent dynamic states of functional connectivity, to identify abnormalities common to epilepsies as well as those specific to each subtype. RESULTS: The analyses revealed that hypervariable edges within the specific DMN subsystem were shared by all subtypes (all PNBS  < .005), and deficits in node-wise temporal variability were prominent in TLE (all t(243) ≤ 2.51, PFDR  < .05) and FLE (all t(302) ≤ -2.65, PFDR  < .05) but relatively weak in GGE-GTCS. Moreover, dynamic states were generally less stable in patients than controls (all P's < .001). SIGNIFICANCE: Collectively, these findings demonstrated general DMN abnormalities common to different epilepsies as well as distinct dysfunctions to subtypes, and provided insights into understanding the relationship of pathophysiological mechanisms and brain connectivity.

Electroclinical features of lateral and medial orbitofrontal epilepsy: a case series.

To better understand the electroclinical features and epileptic network of lateral and medial orbitofrontal epilepsy (OFE). We evaluated four patients who had undergone epilepsy surgery. Epileptic foci in two patients originated from the lateral orbitofrontal cortex, and those in the other two originated from the medial orbitofrontal cortex, which was confirmed by stereoelectroencephalography (SEEG). Time-frequency spectrograms were also provided for assistance, and the change in high-frequency energy was superimposed on the 3D reconstructed brain with a colour code in order to more intuitively show the transfer of high-frequency energy as the seizure evolves. All patients underwent SEEG-guided radiofrequency thermocoagulation (RF-TC) or focal resection and achieved satisfactory results. Lateral OFE and medial OFE were relatively independent with regards to clinical symptoms and epileptic network, however, lateral OFE was likely to propagate to the dorsolateral frontal lobe, whereas medial OFE (gyrus rectus) was more likely to propagate to the medial temporal lobe or insular lobe with long duration. There were significant differences in duration (21.17 ± 11.5 vs. 127.22 ± 235.05) and early propagation time (7.92 ± 4.44 vs. 29.0 ± 33.47) between the two origins. A better understanding of the electroclinical features of lateral and medial OFE is helpful to understand their epileptic networks and perform accurate resections in order to protect the cognitive and behavioural functions of patients.

Association between lack of functional connectivity of the frontal brain region and poor response inhibition in children with frontal lobe epilepsy.

PURPOSE: We investigated the relationship between electroencephalographic (EEG) functional connectivity and executive function in children with frontal lobe epilepsy (FLE). METHODS: We enrolled 24 children with FLE (mean age, 11.0 years; 13 boys) and 22 sex-, age-, and intelligence-matched typically developing children (TDC) to undergo 19-channel EEG during light sleep. We estimated functional connectivity using the phase lag index (PLI) that captures the synchronization of EEG. We also performed continuous performance tests (CPTs) on the children and obtained questionnaire responses on attention deficit hyperactivity disorder and oppositional defiant disorder (ODD). RESULTS: The average gamma PLI was lower in the FLE group than in the TDC group, especially between long-distance frontoparietal pairs, between interhemispheric frontal pairs, and between interhemispheric parietotemporal pairs. Gamma PLIs with long-distance frontoparietal and interhemispheric frontal pairs were positively associated with inattention, ODD scores, omission error, and reaction time in the FLE group but not in the TDC group. Conversely, they were negatively associated with age, hyperactivity score, and commission error. CONCLUSIONS: A lack of functional connectivity of the frontal brain regions in children with FLE was associated with poor response inhibition.

Autosomal dominant lateral temporal lobe epilepsy associated with a novel reelin mutation.

Reelin mutations are responsible for a minority of families with autosomal dominant lateral temporal lobe epilepsy. Here, we report a novel nuclear family with distinct clinical and neuroradiological findings. We studied the proband and her mother by means of EEG, video-EEG, 3T MRI, FDG-PET and genetic testing. Both patients had a focal drug-resistant epilepsy with onset at the age of 16 and focal seizures with typical auditory features combined with fear, followed by loss of contact or evolving to bilateral tonic-clonic seizures. The proband's ictal EEG showed clear left temporal seizure onset, and cerebral MRI revealed subtle left temporal changes (mild hypotrophy, slight blurring of the white and grey matter and hyperintensity) with corresponding left temporal mesial focal hypometabolism on FDG-PET. Genetic testing identified a missense variant, c.6631C>T (p.Arg2211Cys), in reelin repeat #5 in both patients, which markedly affected the secretion of the protein. The data from this family support previous findings indicating that reelin mutations are a cause of autosomal dominant lateral temporal lobe epilepsy which has a clinical spectrum that may also encompass drug-resistant epilepsy associated with mild MRI temporal changes.

Networks in Frontal Lobe Epilepsy.

Epilepsy affects about 1% of the general population. Frontal lobe epilepsy is the second most common focal epilepsy accounting for nearly 25% of medically refractory epilepsies. This paper reviews frontal lobe epilepsy from a perspective of a network disease that may help us to understand epilepsy from the microscale of genes, to local neuronal circuits, to the macrolevel of a whole-brain network. Surgical interventions, such as ablation and resection act by removing the active target nodes in the network, while responsive neurostimulation and vagus nerve stimulation act by modulating networks at the local neuronal circuit level and whole-brain level.

Semiologic subgroups of insulo-opercular seizures based on connectional architecture atlas.

OBJECTIVE: Insulo-opercular seizures are characterized by diverse semiology, related to the insula's multiple functional roles and extensive connectivity. We aimed to identify semiologic subgroups and correlate these with insulo-opercular subregions based on connectional architecture. METHODS: We retrospectively collected a large series of 37 patients with insulo-opercular seizures explored by stereoelectroencephalography (SEEG) from three epilepsy centers. A new human brain atlas (Brainnetome Atlas, BNA) based on both anatomic and functional connections was employed to segment insulo-opercular cortex. Semiology and SEEG changes were carefully reviewed and quantified. Principal component analysis and cluster analysis were used to correlate semiologic characteristics with insulo-opercular subregions. RESULTS: Four main semiologic subgroups were identified, organized along an anteroventral to posterodorsal axis based on BNA. Group 1 was characterized by epigastric sensation and/or integrated gestural motor behaviors with or without feelings of fear or rage, involving the anteroventral insular regions and mesial temporal lobes. Group 2 was characterized by auditory sensations and symmetric proximal/axial tonic signs involving the posteroventral temporal operculum. The characteristics of group 3 were orofacial and laryngeal signs, involving the intermediate insulo-opercular regions. The features of group 4 were somatosensory signs followed by nonintegrated gestural motor behaviors and/or asymmetric tonic signs involving the posterodorsal insulo-opercular regions with propagation to the mesial frontal lobes. Thus anteroventral seizure organizations predominantly showed limbic system semiology, whereas more posterodorsal regions were associated with semiology involving mainly the sensorimotor system. Subjective symptoms proved to be particularly discriminating factors. SIGNIFICANCE: Insulo-opercular seizures can be categorized in terms of clinical semiology and correlate with connectional architecture subregions along an anteroventral-posterodorsal axis in line with the cytoarchitectonic gradient rather than the gyral anatomy of the insula cortex. This provides new insights into facilitating differential diagnosis and presurgical localization but also highlights the importance of considering connectional architecture in determining neural correlates of complex semiologic patterns.

The understanding of mental states and the cognitive phenotype of frontal lobe epilepsy.

OBJECTIVE: Previous studies of frontal lobe epilepsy (FLE) have documented different impairments of theory of mind (ToM), while the study of frontal lobe (FL) lesion without seizures has produced inconsistent results. Given the role played by the FLs in ToM, we evaluated this and other functions in patients with FLE with and without FL lesions. The main objective was to clarify the salience of ToM impairment in the cognitive pattern of FLE and its capacity to discriminate these patients from healthy subjects. The effects of FL lesions on ToM were also explored. METHODS: Seventy-five adult patients with FLE (40 cases with FL lesions) were compared with 42 healthy controls. The Faux Pas Task (FPT) and other neuropsychological tests were utilized to assess ToM, reasoning, language, memory, praxis, attention, and executive abilities. RESULTS: The patients obtained lower z scores for the FPT than for other tests. The ToM, Executive, and Verbal factors discriminated patients from healthy subjects. The patients with or without FL lesion showed significant impairments in recognizing and understanding others' epistemic and affective mental states, but adequate capacity to exclude inexistent mental states was retained. In comparison with controls, the patients with FL lesions obtained lower scores for lexical, memory, praxis, attention, and executive functions, whereas those without lesion only showed attention and initiative deficits. Schooling was the major predictor of ToM, whereas the capacity to exclude inexistent mental states was related to seizure onset age and epilepsy duration. Other cognitive functions were related to schooling, age, or FLE laterality. SIGNIFICANCE: Impaired understanding of real mental states is a specific, salient, and discriminating cognitive aspect of FLE. Poor education is a risk factor for ToM deficit, whereas the clinical variables and FL lesions have no impact. These results suggest that impaired ToM may be a marker of FLE neurobehavioral phenotype.

Sexual functions in women with focal epilepsy: Relationship to demographic, clinical, hormonal and psychological variables.

OBJECTIVES: Sexual dysfunctions [SDs] are common in women with epilepsy [WWE] but related studies were neglected in our locality. We aimed to determine the frequencies and severities of SDs and their clinical, hormonal and psychological determinants in WWE. PATIENTS AND METHODS: This study included 120 adults [mean age: 36.35 ± 2.89yrs] with temporal [63.33 %] and frontal [36.67 %] lobe epilepsies and treated with carbamazepine [CBZ] [n = 60] or oxcarbazepine [OXC] [n = 60] for mean duration of 18.63 ± 4.33yrs. Patients were assessed using Female Sexual Function Index [FSFI] questionnaire, Beck Depression Inventory [BDI-II] and Hamilton Anxiety Rating Scale [HAM-A]. Total testosterone, sex hormone binding globulin [SHBG] and free androgen index [FAI] were measured to assess endocrinal status. PATIENTS AND METHODS: This study included 120 adults [mean age: 36.35 ± 2.89yrs] with temporal [63.33 %] and frontal [36.67 %] lobe epilepsies and treated with carbamazepine [CBZ] [n = 60] or oxcarbazepine [OXC] [n = 60] for mean duration of 18.63 ± 4.33yrs. Patients were assessed using Female Sexual Function Index [FSFI] questionnaire, Beck Depression Inventory [BDI-II] and Hamilton Anxiety Rating Scale [HAM-A]. Total testosterone, sex hormone binding globulin [SHBG] and free androgen index [FAI] were measured to assess endocrinal status. RESULTS: The majority had occasional/rare frequency of seizures [76.67 %] and well controlled on antiepileptic drugs [AEDs] [81.67 %]. Compared to healthy women, WWE had lower total testosterone and FAI and higher SHBG levels. Compared to women on CBZ, those on OXC had lower frequency and well controlled seizures on medication [P = 0.0001 for both], higher testosterone [P = 0.01] and FAI [P = 0.001] and lower SHBG [P = 0.001] levels. Compared to controls, WWE had significantly higher frequencies and severities of SDs [total sexual function, desire, arousal, lubrication, orgasm, satisfaction and pain] and depression and anxiety symptoms. OXC therapy was associated with lower SDs [FSFI: P = 0.033] and anxiety symptoms [P = 0.025] compared to CBZ therapy. In multiple logistic regression analyses, determinants of SDs were the higher seizures frequency, increasing severities of depression and anxiety but not lower androgen levels or type of epilepsy or AEDs. CONCLUSIONS: Different aspects of SD and depression and anxiety symptoms were frequent in WWE. Determinants of SDs were the higher frequency of seizures and increasing severities of depression and anxiety. OXC had better control on seizures and thus lower frequencies and severities of SDs and depression and anxiety symptoms. Thus optimizing seizure control is important for psychological state and healthy sexual function in WWE.

Neuroimaging of memory in frontal lobe epilepsy.

In a large percentage of epilepsies, seizures have focal onset. These epilepsies are associated with a wide range of behavioral and cognitive deficits sometimes limited to the functions encompassed within the ictal onset zone but, more frequently, expanding beyond it. The presence of impairments associated with neuroanatomical areas outside of the ictal onset zone suggests distal propagation of epileptic activity via brain networks and interconnected whole-brain neural circuitry. In patients with frontal lobe epilepsy (FLE), using functional magnetic resonance imaging (fMRI) to identify deficits in working, semantic, and episodic memory may provide a lens through which to understand typical and atypical network organization. A network approach to focal epilepsy is relevant in these patients because of the frequently noted early age of seizure onset. Early seizure-related disruption in healthy brain development may result in a significant brain reorganization, development of compensation-related mechanisms of dealing with function abnormalities and disruptions, and the propagation of epileptic activity from the focus to widespread brain areas (functional deficit zones). Benefits of a network approach in the study of focal epilepsy are discussed along with considerations for future neuroimaging studies of patients with FLE.